The proposed COBRE will focus a diverse group of scientists on a central mission?to enable discovery of new therapeutic leads and molecules that probe the function of biological targets. This COBRE represents a new scientific direction for the University of Delaware (UD), and researchers in the center will develop methods for creating, screening and analyzing probe molecules and their biological targets on a scale that cannot be supported by existing core instrumentation. Accordingly, a research core of considerable infrastructure will be created in order to promote the success ofthe center. This COBRE will establish a Screening, Analysis and Synthesis (SAS) Research Core that facilitates high throughput synthesis and rapid purification of molecular libraries. The SAS core will enable printing libraries of immunostimulatory molecules and the creation of ultra-sensitive detection methods for chip-based binding assays. The SAS will house instrumentation for the high throughput assessment of cell response to small molecules and will facilitate the creation of the first in vitro assay for Huntington's disease. A plan for the oversight and maintenance ofthe SAS core is outlined. This COBRE will also enable the discovery of computational methods that are capable of permitting lead structures to be predicted and optimized in a rational manner. To facilitate the intensive computation that will be needed, we will expand an existing IDeA-funded computational cluster with the addition of 504 compute cores. The cluster is designed to be suited for highly parallel molecular dynamics, density functional theory calculations, and high throughput virtual screening. A plan for oversight and maintenance ofthe computational core is outlined.